This grant application proposes to further develop and evaluate an extracorporeal respiratory support device based on a new yet well-established principle. This device achieves respiratory gas exchange by transporting across a hemodialysis membrane highly water soluble derivatives of the respiratory gases, namely hydrogen peroxide and bicarbonate ion. The associated accumulation in the blood of buffered hydrogen ion is neutralized by absorption of hydroxyl ion from the dialysis bath. Oxygenation is achieved by transmembrane catalysis of hydrogen peroxide. The dialyzer acts as a built-in heat exchanger. A multidisciplinary program to design and evaluate this extracorporeal device for a variety of clinical uses is proposed, including the treatment of severe acute respiratory failure and respiratory support during surgery requiring cardiopulmonary bypass. Because the device is based on hemodialysis principles, artificial kidney treatment and stabilization of acid-base status can be accomplished at the same time total respiratory support is provided. As part of the development of this device, basic research will be conducted on relevant aspects of membrane materials, biocompatibility, and heterogeneous phase membrane catalysis of H2O2.